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  • 标题:Risk Estimation with Epidemiologic Data When Response Attenuates at High-Exposure Levels
  • 作者:Kyle Steenland ; Ryan Seals ; Mitch Klein
  • 期刊名称:Environmental Health Perspectives
  • 印刷版ISSN:0091-6765
  • 电子版ISSN:1552-9924
  • 出版年度:2011
  • 卷号:119
  • 期号:6
  • 页码:831-837
  • DOI:10.1289/ehp.1002521
  • 语种:English
  • 出版社:OCR Subscription Services Inc
  • 摘要:Background In occupational studies, which are commonly used for risk assessment for environmental settings, estimated exposure–response relationships often attenuate at high exposures. Relative risk (RR) models with transformed (e.g., log- or square root–transformed) exposures can provide a good fit to such data, but resulting exposure–response curves that are supralinear in the low-dose region may overestimate low-dose risks. Conversely, a model of untransformed (linear) exposure may underestimate risks attributable to exposures in the low-dose region. Methods We examined several models, seeking simple parametric models that fit attenuating exposure–response data well. We have illustrated the use of both log-linear and linear RR models using cohort study data on breast cancer and exposure to ethylene oxide. Results Linear RR models fit the data better than do corresponding log-linear models. Among linear RR models, linear (untransformed), log-transformed, square root–transformed, linear-exponential, and two-piece linear exposure models all fit the data reasonably well. However, the slopes of the predicted exposure–response relations were very different in the low-exposure range, which resulted in different estimates of the exposure concentration associated with a 1% lifetime excess risk (0.0400, 0.00005, 0.0016, 0.0113, and 0.0100 ppm, respectively). The linear (in exposure) model underestimated the categorical exposure–response in the low-dose region, whereas log-transformed and square root–transformed exposure models overestimated it. Conclusion Although a number of models may fit attenuating data well, models that assume linear or nearly linear exposure–response relations in the low-dose region of interest may be preferred by risk assessors, because they do not depend on the choice of a point of departure for linear low-dose extrapolation and are relatively easy to interpret.
  • 关键词:ethylene oxide; risk assessment; statistical models
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